128
RECENT
EFFICACY DATA OF TOLTRAZURIL AGAINST
TURKEY
COCCIDIOSIS IN CAGE AND FLOOR PEN STUDIES
R. Froyman, T.
Irion and G. Greif
Bayer Animal
Health Business Group, D-51368 Leverkusen, Germany
Adequate control
of coccidiosis remains a continuing turkey health topic. Apart
from increased
mortality, E. meleagrimitis and E. adenoeides, the 2 most
common pathogenic Eimeria
species, provoke clinical disease with reduced
feed intake and
decreased performance (Edgar, 1987; McDougald, 1998).
Despite improving
husbandry standards and the strategic use of in-feed
anticoccidials,
clinical outbreaks still occur and are encountered in growing
turkeys, commonly
between 3 and 5 weeks of age. Early Haemorrhagic
Enteritis (HE)
infections, HE vaccination, flock relocation or transition from
starter to grower
feed are reported as triggering agents. Hence there is a need
for efficacious
anticoccidial drugs to treat coccidiosis in the drinking water.
Toltrazuril
(Baycoxâ), a symmetrical
triazinetrione, is a recognised compound
for the treatment
of coccidiosis infections in poultry and mammals. Since many
years Baycox has a
proven record of efficacy against chicken and turkey
coccidiosis in the
field.
The efficacy of
toltrazuril has been shown in multiple controlled studies (Greuel
et al., 1989; Greuel et
al., 1991; Pashov and Koinarski, 1994). These trials
consisted of
artificial challenges with E. meleagrimitis, E. adenoeides and/or E.
gallopavonis in 2 week old
turkeys followed by one or two treatment courses
with 25 ppm
toltrazuril in the drinking water for 2 consecutive days. The aim of
the work reported
here was to confirm the efficacy of a single two day treatment
course with Baycox
at the recommended daily dose of 7 mg/kg and to examine
whether increasing
this dose would improve efficacy. An artificial challenge
model was
developed in house, compliant to GCP guidelines, to the specific EU
Directive
(81/852/EEC, Ref. 111/9289/90) for anticoccidials used for the therapy
of coccidiosis in
turkeys and geese, and to the FDA guidance
(guideline “40” for
evaluating the efficacy of anticoccidial drugs) . In this challenge
model 10 to 12
day old turkey poults were challenged with reference Eimeria isolates of known
pathogenicity (CVL, Weybridge, UK), kindly provided by R. Marshall. The
coccidiosis infections, either E. meleagrimitis or E. adenoeides, were titrated in
susceptible turkey poults in order to define an infectious inoculum of
sporulated
oocysts that provoked approx. 50 % weight loss compared to untreated,
unchallenged controls. Challenge doses varied between 50,000 and 100,000
oocysts for E. meleagrimitis and between 5,000 and 12,500 for E. adenoeides.
In the dose response studies dose ranges of toltrazuril varying between
3 and
14 mg/kg were compared against negative controls (not infected, not
treated)
and positive controls (infected, not treated). All experimental
treatments were
129
replicated twice
in cages or pens of 5 to 12 poults each. Toltrazuril was given in
the drinking water
at days 2 and 3 post infection (PI). Weight gain and oocyst
counts were the
pivotal efficacy criteria monitored. In our hands intestinal lesion
scoring, which is
in turkeys far less specific and standardised than in chickens,
was not a very
useful diagnostic tool. Our experience confirmed the FDA
efficacy guideline
(www.fda.gov) which states that, in turkeys, body weight gain
is the most
appropriate predictor and lesion scoring a poor predictor of the
severity of a
coccidiosis infection. Faecal oocysts were counted between 4 and
7 days PI and
final body weights were measured one day later. All together four
studies were run,
one in cages, three others in floor pens.
With both Eimeria
spp. the experimental challenge produced overt clinical
disease in the
positive controls with total faecal oocyst outputs (number/g) of
approx. 4 to 7
log10, mostly about 6 log10, and weight gain reductions
compared to the
negative controls of 32 to 65%, on average 60 % for E.
meleagrimitis and 38 % for E.
adenoeides. Over the entire toltrazuril dose range
tested oocyst
excretion remained below the limit of detection (67 oocyst/g). In
contrast to the
severe growth depression observed in the positive controls,
weight gain of the
turkey poults treated with 7 mg toltrazuril/kg for 2 days was
very close to this
of the negative controls, i.e. at 77 to 97 % for E. meleagrimitis
and at 93 to 99 %
for E. adenoeides. Increasing the dose from 7 to 10 or 14
mg/kg did not
improve control of challenge induced weight gain depression.
The results of
these 4 dose response trials were compared with those of similar
work conducted 5
years before (Roux, 1997). In the latter 2 battery dose
titration studies,
the recommended dose of 7 mg/kg of a single two-day Baycox
treatment course
was assessed against 14 and 21 mg/kg. Optimum efficacy
was shown for E.
meleagrimitis as well as E. adenoeides at 7 mg/kg with
weight
gains of 98 to 99
% compared to the negative controls and with full reduction of
oocyst shedding.
Doubling or tripling the recommended 7 mg/kg dose did not
boost efficacy.
The current trials and those of Roux (1997) allow to conclude
that a single
treatment course of 2 days with Baycox in drinking water at 7
mg/kg is the
reliable, fully efficacious dosage to control outbreaks of turkey
occidiosis.
As a toltrazuril
dosage increase beyond the recommended label claim does not
improve clinical
efficacy, we assume that an inherent lack of activity of this
compound is not a
likely cause of suspected treatment failures. Should
incidentally
treatment failures occur then other factors should be considered,
e.g. intercurrent
disease, interfering bacterial complications,
immunesuppression,
wrong diagnosis, inappropriate dosing, or a combinations
thereof. To learn
more about possible product related treatment failures we
conducted very
recently an inquiry in Europe. We found out that occasionally
cases were
reported in situations when Baycox was dosed on a 25 ppm in
water basis .
Actually true therapy failures were never encountered when the
product was dosed
on a 7 mg/kg basis. Although under “regular” husbandry
conditions a 25 ppm dosage in the drinking water ( 1 L. Baycoxâ 2.5 % oral
solution/1000 L. water) is close to the daily recommended dose of 7 mg
toltrazuril/kg in 2 week old turkeys, an underdosage of about 20, 40 and
50 %
may be expected in turkeys aged 3, 5 and 7 weeks, respectively.
130
Repeated dose and
overdose animal safety trials in turkeys have shown that
Baycox at the
recommended dosage has no significant effect on drug
palatabilty and
bird performance. Doses up to 35 to 40 mg/kg for 2 days were
well tolerated
(blood chemistry, performance). Other studies (Depta, 1985;
Mitschke, 1988)
suggest or indicate that toltrazuril palatability is not significantly
impaired at
drinking water dosages corresponding to daily doses lower than a
threefold overdose
(21 mg/kg). All in all Baycox administered at the
recommended dosage
is a very efficacious and safe drug for the treatment of
coccidiosis in
growing turkeys.
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